Project acronym 2DNanoSpec
Project Nanoscale Vibrational Spectroscopy of Sensitive 2D Molecular Materials
Researcher (PI) Renato ZENOBI
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE4, ERC-2016-ADG
Summary I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Summary
I propose to investigate the nanometer scale organization of delicate 2-dimensional molecular materials using nanoscale vibrational spectroscopy. 2D structures are of great scientific and technological importance, for example as novel materials (graphene, MoS2, WS2, etc.), and in the form of biological membranes and synthetic 2D-polymers. Powerful methods for their analysis and imaging with molecular selectivity and sufficient spatial resolution, however, are lacking. Tip-enhanced Raman spectroscopy (TERS) allows label-free spectroscopic identification of molecular species, with ≈10 nm spatial resolution, and with single molecule sensitivity for strong Raman scatterers. So far, however, TERS is not being carried out in liquids, which is the natural environment for membranes, and its application to poor Raman scatterers such as components of 2D polymers, lipids, or other membrane compounds (proteins, sugars) is difficult. TERS has the potential to overcome the restrictions of other optical/spectroscopic methods to study 2D materials, namely (i) insufficient spatial resolution of diffraction-limited optical methods; (ii) the need for labelling for all methods relying on fluorescence; and (iii) the inability of some methods to work in liquids. I propose to address a number of scientific questions associated with the spatial organization, and the occurrence of defects in sensitive 2D molecular materials. The success of these studies will also rely critically on technical innovations of TERS that notably address the problem of energy dissipation. This will for the first time allow its application to study of complex, delicate 2D molecular systems without photochemical damage.
Max ERC Funding
2 311 696 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym AGRISCENTS
Project Scents and sensibility in agriculture: exploiting specificity in herbivore- and pathogen-induced plant volatiles for real-time crop monitoring
Researcher (PI) Theodoor Turlings
Host Institution (HI) UNIVERSITE DE NEUCHATEL
Call Details Advanced Grant (AdG), LS9, ERC-2017-ADG
Summary Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Summary
Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Max ERC Funding
2 498 086 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym AlgoRNN
Project Recurrent Neural Networks and Related Machines That Learn Algorithms
Researcher (PI) Juergen Schmidhuber
Host Institution (HI) UNIVERSITA DELLA SVIZZERA ITALIANA
Call Details Advanced Grant (AdG), PE6, ERC-2016-ADG
Summary Recurrent neural networks (RNNs) are general parallel-sequential computers. Some learn their programs or weights. Our supervised Long Short-Term Memory (LSTM) RNNs were the first to win pattern recognition contests, and recently enabled best known results in speech and handwriting recognition, machine translation, etc. They are now available to billions of users through the world's most valuable public companies including Google and Apple. Nevertheless, in lots of real-world tasks RNNs do not yet live up to their full potential. Although universal in theory, in practice they fail to learn important types of algorithms. This ERC project will go far beyond today's best RNNs through novel RNN-like systems that address some of the biggest open RNN problems and hottest RNN research topics: (1) How can RNNs learn to control (through internal spotlights of attention) separate large short-memory structures such as sub-networks with fast weights, to improve performance on many natural short-term memory-intensive tasks which are currently hard to learn by RNNs, such as answering detailed questions on recently observed videos? (2) How can such RNN-like systems metalearn entire learning algorithms that outperform the original learning algorithms? (3) How to achieve efficient transfer learning from one RNN-learned set of problem-solving programs to new RNN programs solving new tasks? In other words, how can one RNN-like system actively learn to exploit algorithmic information contained in the programs running on another? We will test our systems existing benchmarks, and create new, more challenging multi-task benchmarks. This will be supported by a rather cheap, GPU-based mini-brain for implementing large RNNs.
Summary
Recurrent neural networks (RNNs) are general parallel-sequential computers. Some learn their programs or weights. Our supervised Long Short-Term Memory (LSTM) RNNs were the first to win pattern recognition contests, and recently enabled best known results in speech and handwriting recognition, machine translation, etc. They are now available to billions of users through the world's most valuable public companies including Google and Apple. Nevertheless, in lots of real-world tasks RNNs do not yet live up to their full potential. Although universal in theory, in practice they fail to learn important types of algorithms. This ERC project will go far beyond today's best RNNs through novel RNN-like systems that address some of the biggest open RNN problems and hottest RNN research topics: (1) How can RNNs learn to control (through internal spotlights of attention) separate large short-memory structures such as sub-networks with fast weights, to improve performance on many natural short-term memory-intensive tasks which are currently hard to learn by RNNs, such as answering detailed questions on recently observed videos? (2) How can such RNN-like systems metalearn entire learning algorithms that outperform the original learning algorithms? (3) How to achieve efficient transfer learning from one RNN-learned set of problem-solving programs to new RNN programs solving new tasks? In other words, how can one RNN-like system actively learn to exploit algorithmic information contained in the programs running on another? We will test our systems existing benchmarks, and create new, more challenging multi-task benchmarks. This will be supported by a rather cheap, GPU-based mini-brain for implementing large RNNs.
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym Amygdala Circuits
Project Amygdala Circuits for Appetitive Conditioning
Researcher (PI) Andreas Luthi
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Call Details Advanced Grant (AdG), LS5, ERC-2014-ADG
Summary The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.
Summary
The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.
Max ERC Funding
2 497 200 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym ANOBEST
Project Structure function and pharmacology of calcium-activated chloride channels: Anoctamins and Bestrophins
Researcher (PI) Raimund Dutzler
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS1, ERC-2013-ADG
Summary Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.
Summary
Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.
Max ERC Funding
2 176 000 €
Duration
Start date: 2014-02-01, End date: 2020-01-31
Project acronym Antivessel-T-Cells
Project Development of Vascular-Disrupting Lymphocyte Therapy for Tumours
Researcher (PI) Georgios Coukos
Host Institution (HI) CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS
Call Details Advanced Grant (AdG), LS7, ERC-2012-ADG_20120314
Summary T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Summary
T cell engineering with chimeric antigen receptors has opened the door to effective immunotherapy. CARs are fusion genes encoding receptors whose extracellular domain comprises a single chain variable fragment (scFv) antibody that binds to a tumour surface epitope, while the intracellular domain comprises the signalling module of CD3ζ along with powerful costimulatory domains (e.g. CD28 and/or 4-1BB). CARs are a major breakthrough, since they allow bypassing HLA restrictions or loss, and they can incorporate potent costimulatory signals tailored to optimize T cell function. However, solid tumours present challenges, since they are often genetically unstable, and the tumour microenvironment impedes T cell function. The tumour vasculature is a much more stable and accessible target, and its disruption has catastrophic consequences for tumours. Nevertheless, the lack of affinity reagents has impeded progress in this area. The objectives of this proposal are to develop the first potent and safe tumour vascular-disrupting tumour immunotherapy using scFv’s and CARs uniquely available in my laboratory.
I propose to use these innovative CARs to understand for the first time the molecular mechanisms underlying the interactions between anti-vascular CAR-T cells and tumour endothelium, and exploit them to maximize tumour vascular destruction. I also intend to employ innovative engineering approaches to minimize the chance of reactivity against normal vasculature. Lastly, I propose to manipulate the tumour damage mechanisms ensuing anti-vascular therapy, to maximize tumour rejection through immunomodulation. We are poised to elucidate critical interactions between tumour endothelium and anti-vascular T cells, and bring to bear cancer therapy of unparalleled power. The impact of this work could be transforming, given the applicability of tumour-vascular disruption across most common tumour types.
Max ERC Funding
2 500 000 €
Duration
Start date: 2013-08-01, End date: 2018-07-31
Project acronym AOC
Project Adversary-Oriented Computing
Researcher (PI) Rachid Guerraoui
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE6, ERC-2013-ADG
Summary "Recent technological evolutions, including the cloud, the multicore, the social and the mobiles ones, are turning computing ubiquitously distributed. Yet, building high-assurance distributed programs is notoriously challenging. One of the main reasons is that these systems usually seek to achieve several goals at the same time. In short, they need to be efficient, responding effectively in various average-case conditions, as well as reliable, behaving correctly in severe, worst-case conditions. As a consequence, they typically intermingle different strategies: each to cope with some specific condition, e.g., with or without node failures, message losses, time-outs, contention, cache misses,
over-sizing, malicious attacks, etc. The resulting programs end up hard to design, prove, verify, implement, test and debug. Not surprisingly, there are anecdotal evidences of the fragility of the most celebrated distributed systems.
The goal of this project is to contribute to building high-assurance distributed programs by introducing a new dimension for separating and isolating their concerns, as well as a new scheme for composing and reusing them in a modular manner. In short, the project will explore the inherent power and limitations of a novel paradigm, Adversary-Oriented Computing (AOC). Sub-programs, each implementing a specific strategy to cope with a given adversary, modelling a specific working condition, are designed, proved, verified, implemented, tested and debugged independently. They are then composed, possibly dynamically, as black-boxes within the same global program. The AOC project is ambitious and it seeks to fundamentally revisit the way distributed algorithms are designed and distributed systems are implemented. The gain expected in comparison with today's approaches is substantial, and I believe it will be proportional to the degree of difficulty of the distributed problem at hand."
Summary
"Recent technological evolutions, including the cloud, the multicore, the social and the mobiles ones, are turning computing ubiquitously distributed. Yet, building high-assurance distributed programs is notoriously challenging. One of the main reasons is that these systems usually seek to achieve several goals at the same time. In short, they need to be efficient, responding effectively in various average-case conditions, as well as reliable, behaving correctly in severe, worst-case conditions. As a consequence, they typically intermingle different strategies: each to cope with some specific condition, e.g., with or without node failures, message losses, time-outs, contention, cache misses,
over-sizing, malicious attacks, etc. The resulting programs end up hard to design, prove, verify, implement, test and debug. Not surprisingly, there are anecdotal evidences of the fragility of the most celebrated distributed systems.
The goal of this project is to contribute to building high-assurance distributed programs by introducing a new dimension for separating and isolating their concerns, as well as a new scheme for composing and reusing them in a modular manner. In short, the project will explore the inherent power and limitations of a novel paradigm, Adversary-Oriented Computing (AOC). Sub-programs, each implementing a specific strategy to cope with a given adversary, modelling a specific working condition, are designed, proved, verified, implemented, tested and debugged independently. They are then composed, possibly dynamically, as black-boxes within the same global program. The AOC project is ambitious and it seeks to fundamentally revisit the way distributed algorithms are designed and distributed systems are implemented. The gain expected in comparison with today's approaches is substantial, and I believe it will be proportional to the degree of difficulty of the distributed problem at hand."
Max ERC Funding
2 147 012 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym astromnesis
Project The language of astrocytes: multilevel analysis to understand astrocyte communication and its role in memory-related brain operations and in cognitive behavior
Researcher (PI) Andrea Volterra
Host Institution (HI) UNIVERSITE DE LAUSANNE
Call Details Advanced Grant (AdG), LS5, ERC-2013-ADG
Summary In the 90s, two landmark observations brought to a paradigm shift about the role of astrocytes in brain function: 1) astrocytes respond to signals coming from other cells with transient Ca2+ elevations; 2) Ca2+ transients in astrocytes trigger release of neuroactive and vasoactive agents. Since then, many modulatory astrocytic actions and mechanisms were described, forming a complex - partly contradictory - picture, in which the exact roles and modes of astrocyte action remain ill defined. Our project wants to bring light into the “language of astrocytes”, i.e. into how they communicate with neurons and, ultimately, address their role in brain computations and cognitive behavior. To this end we will perform 4 complementary levels of analysis using highly innovative methodologies in order to obtain unprecedented results. We will study: 1) the subcellular organization of astrocytes underlying local microdomain communications by use of correlative light-electron microscopy; 2) the way individual astrocytes integrate inputs and control synaptic ensembles using 3D two-photon imaging, genetically-encoded Ca2+ indicators, optogenetics and electrophysiology; 3) the contribution of astrocyte ensembles to behavior-relevant circuit operations using miniaturized microscopes capturing neuronal/astrocytic population dynamics in freely-moving mice during memory tests; 4) the contribution of astrocytic signalling mechanisms to cognitive behavior using a set of new mouse lines with conditional, astrocyte-specific genetic modification of signalling pathways. We expect that this combination of groundbreaking ideas, innovative technologies and multilevel analysis makes our project highly attractive to the neuroscience community at large, bridging aspects of molecular, cellular, systems and behavioral neuroscience, with the goal of leading from a provocative hypothesis to the conclusive demonstration of whether and how “the language of astrocytes” participates in memory and cognition.
Summary
In the 90s, two landmark observations brought to a paradigm shift about the role of astrocytes in brain function: 1) astrocytes respond to signals coming from other cells with transient Ca2+ elevations; 2) Ca2+ transients in astrocytes trigger release of neuroactive and vasoactive agents. Since then, many modulatory astrocytic actions and mechanisms were described, forming a complex - partly contradictory - picture, in which the exact roles and modes of astrocyte action remain ill defined. Our project wants to bring light into the “language of astrocytes”, i.e. into how they communicate with neurons and, ultimately, address their role in brain computations and cognitive behavior. To this end we will perform 4 complementary levels of analysis using highly innovative methodologies in order to obtain unprecedented results. We will study: 1) the subcellular organization of astrocytes underlying local microdomain communications by use of correlative light-electron microscopy; 2) the way individual astrocytes integrate inputs and control synaptic ensembles using 3D two-photon imaging, genetically-encoded Ca2+ indicators, optogenetics and electrophysiology; 3) the contribution of astrocyte ensembles to behavior-relevant circuit operations using miniaturized microscopes capturing neuronal/astrocytic population dynamics in freely-moving mice during memory tests; 4) the contribution of astrocytic signalling mechanisms to cognitive behavior using a set of new mouse lines with conditional, astrocyte-specific genetic modification of signalling pathways. We expect that this combination of groundbreaking ideas, innovative technologies and multilevel analysis makes our project highly attractive to the neuroscience community at large, bridging aspects of molecular, cellular, systems and behavioral neuroscience, with the goal of leading from a provocative hypothesis to the conclusive demonstration of whether and how “the language of astrocytes” participates in memory and cognition.
Max ERC Funding
2 513 896 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym AtomicGaugeSimulator
Project Classical and Atomic Quantum Simulation of Gauge Theories in Particle and Condensed Matter Physics
Researcher (PI) Uwe-Jens Richard Christian Wiese
Host Institution (HI) UNIVERSITAET BERN
Call Details Advanced Grant (AdG), PE2, ERC-2013-ADG
Summary Gauge theories play a central role in particle and condensed matter physics. Heavy-ion collisions explore the strong dynamics of quarks and gluons, which also governs the deep interior of neutron stars, while strongly correlated electrons determine the physics of high-temperature superconductors and spin liquids. Numerical simulations of such systems are often hindered by sign problems. In quantum link models - an alternative formulation of gauge theories developed by the applicant - gauge fields emerge from discrete quantum variables. In the past year, in close collaboration with atomic physicists, we have established quantum link models as a framework for the atomic quantum simulation of dynamical gauge fields. Abelian gauge theories can be realized with Bose-Fermi mixtures of ultracold atoms in an optical lattice, while non-Abelian gauge fields arise from fermionic constituents embodied by alkaline-earth atoms. Quantum simulators, which do not suffer from the sign problem, shall be constructed to address non-trivial dynamics, including quantum phase transitions in spin liquids, the real-time dynamics of confining strings as well as of chiral symmetry restoration at finite temperature and baryon density, baryon superfluidity, or color-flavor locking. New classical simulation algorithms shall be developed in order to solve severe sign problems, to investigate confining gauge theories, and to validate the proposed quantum simulators. Starting from U(1) and SU(2) gauge theories, an atomic physics tool box shall be developed for quantum simulation of gauge theories of increasing complexity, ultimately aiming at 4-d Quantum Chromodynamics (QCD). This project is based on innovative ideas from particle, condensed matter, and computational physics, and requires an interdisciplinary team of researchers. It has the potential to drastically increase the power of simulations and to address very challenging problems that cannot be solved with classical simulation methods.
Summary
Gauge theories play a central role in particle and condensed matter physics. Heavy-ion collisions explore the strong dynamics of quarks and gluons, which also governs the deep interior of neutron stars, while strongly correlated electrons determine the physics of high-temperature superconductors and spin liquids. Numerical simulations of such systems are often hindered by sign problems. In quantum link models - an alternative formulation of gauge theories developed by the applicant - gauge fields emerge from discrete quantum variables. In the past year, in close collaboration with atomic physicists, we have established quantum link models as a framework for the atomic quantum simulation of dynamical gauge fields. Abelian gauge theories can be realized with Bose-Fermi mixtures of ultracold atoms in an optical lattice, while non-Abelian gauge fields arise from fermionic constituents embodied by alkaline-earth atoms. Quantum simulators, which do not suffer from the sign problem, shall be constructed to address non-trivial dynamics, including quantum phase transitions in spin liquids, the real-time dynamics of confining strings as well as of chiral symmetry restoration at finite temperature and baryon density, baryon superfluidity, or color-flavor locking. New classical simulation algorithms shall be developed in order to solve severe sign problems, to investigate confining gauge theories, and to validate the proposed quantum simulators. Starting from U(1) and SU(2) gauge theories, an atomic physics tool box shall be developed for quantum simulation of gauge theories of increasing complexity, ultimately aiming at 4-d Quantum Chromodynamics (QCD). This project is based on innovative ideas from particle, condensed matter, and computational physics, and requires an interdisciplinary team of researchers. It has the potential to drastically increase the power of simulations and to address very challenging problems that cannot be solved with classical simulation methods.
Max ERC Funding
1 975 242 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym Attoclock
Project Clocking fundamental attosecond electron dynamics
Researcher (PI) Ursula Keller
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE2, ERC-2012-ADG_20120216
Summary The attoclock is a powerful, new, and unconventional tool to study fundamental attosecond dynamics on an atomic scale. We established its potential by using the first attoclock to measure the tunneling delay time in laser-induced ionization of helium and argon atoms, with surprising results. Building on these first proof-of-principle measurements, I propose to amplify and expand this tool concept to explore the following key questions: How fast can light liberate electrons from a single atom, a single molecule, or a solid-state system? Related are more questions: How fast can an electron tunnel through a potential barrier? How fast is a multi-photon absorption process? How fast is single-photon photoemission? Many of these questions will undoubtedly spark more questions – revealing deeper and more detailed insights on the dynamics of some of the most fundamental and relevant optoelectronic processes.
There are still many unknown and unexplored areas here. Theory has failed to offer definitive answers. Simulations based on the exact time-dependent Schrödinger equation have not been possible in most cases. Therefore one uses approximations and simpler models to capture the essential physics. Such semi-classical models potentially will help to understand attosecond energy and charge transport in larger molecular systems. Indeed the attoclock provides a unique tool to explore different semi-classical models.
For example, the question of whether electron tunneling through an energetically forbidden region takes a finite time or is instantaneous has been subject to ongoing debate for the last sixty years. The tunnelling process, charge transfer, and energy transport all play key roles in electronics, energy conversion, chemical and biological reactions, and fundamental processes important for improved information, health, and energy technologies. We believe the attoclock can help refine and resolve key models for many of these important underlying attosecond processes.
Summary
The attoclock is a powerful, new, and unconventional tool to study fundamental attosecond dynamics on an atomic scale. We established its potential by using the first attoclock to measure the tunneling delay time in laser-induced ionization of helium and argon atoms, with surprising results. Building on these first proof-of-principle measurements, I propose to amplify and expand this tool concept to explore the following key questions: How fast can light liberate electrons from a single atom, a single molecule, or a solid-state system? Related are more questions: How fast can an electron tunnel through a potential barrier? How fast is a multi-photon absorption process? How fast is single-photon photoemission? Many of these questions will undoubtedly spark more questions – revealing deeper and more detailed insights on the dynamics of some of the most fundamental and relevant optoelectronic processes.
There are still many unknown and unexplored areas here. Theory has failed to offer definitive answers. Simulations based on the exact time-dependent Schrödinger equation have not been possible in most cases. Therefore one uses approximations and simpler models to capture the essential physics. Such semi-classical models potentially will help to understand attosecond energy and charge transport in larger molecular systems. Indeed the attoclock provides a unique tool to explore different semi-classical models.
For example, the question of whether electron tunneling through an energetically forbidden region takes a finite time or is instantaneous has been subject to ongoing debate for the last sixty years. The tunnelling process, charge transfer, and energy transport all play key roles in electronics, energy conversion, chemical and biological reactions, and fundamental processes important for improved information, health, and energy technologies. We believe the attoclock can help refine and resolve key models for many of these important underlying attosecond processes.
Max ERC Funding
2 319 796 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
